White Matter Viral Vector Delivery via Convection-Enhanced Diffusion
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for delivering therapeutic agents to the cerebral cortex and spinal cord are challenging due to the difficulty in targeting specific areas of the cortex and the risks associated with intracerebral injections and intrathecal delivery, particularly for neurological disorders like Alzheimer's disease and multiple sclerosis.
Innovation Solution
Convection-enhanced delivery of viral vectors, such as AAV, into the white matter of the brain below targeted cortical regions allows for axonal transport to the cerebral cortex and spinal cord, enabling targeted delivery of therapeutic agents to specific areas like the motor, visual, or auditory cortex and the spinal cord.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intracerebral injection of viral vectors into grey matter structures is used, then therapeutic agents can be delivered to the cerebral cortex, but the procedure is complex and carries increased risks of complications such as haemorrhage
Solution Approach 1:
Instead of injecting directly into the cerebral cortex (grey matter), the patent inverts the approach by injecting into the underlying white matter. The viral vectors are administered into white matter tracts, which then transport the vectors to the cerebral cortex through axonal transport, achieving the same therapeutic effect with reduced surgical complexity and lower hemorrhage risk.
Solution Approach 2:
The patent uses white matter tracts as an intermediary medium to deliver viral vectors to the cerebral cortex. By injecting into the white matter, the vectors utilize the existing axonal transport pathways as a natural delivery system, avoiding the need for precise direct cortical injection and reducing surgical risks.
2Measurement precision
If convection-enhanced delivery is used to target specific thalamic nuclei, then therapeutic agents can be delivered to limited areas of cortex, but the thalamic nuclei are not easily identified with conventional imaging methods
Solution Approach 1:
Instead of attempting to visualize and target deep thalamic nuclei which are invisible to conventional imaging, the patent inverts the approach by targeting the overlying white matter regions that are visible and accessible. The white matter injection sites are positioned to correspond with the desired cortical target areas, allowing precise targeting without the need to visualize deep thalamic structures.
3Ease of operation
If intrathecal delivery of therapeutic agents is used, then the procedure is simple, but it is associated with a large number of side effects such as nausea and dizziness
Solution Approach 1:
The patent extracts the therapeutic delivery from the general intrathecal space and localizes it to specific white matter tracts underlying the target cortical regions. By using convection-enhanced delivery through implanted catheters positioned in the white matter, the method maintains procedural simplicity while eliminating the systemic side effects associated with intrathecal delivery, as the therapy is delivered locally to the target area without widespread distribution.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method achieves targeted delivery of therapeutic agents to the cerebral cortex and spinal cord without systemic exposure, reducing the risk of complications and improving the efficacy of treatments for neurological disorders by utilizing convection-enhanced diffusion through implanted catheters.
Implementation Method 1
Convection-enhanced delivery (CED) describes a method of direct drug delivery to the brain though intraparenchymal microcatheters along an infusion-mediated pressure gradient
Implementation Method 2
along an infusion-mediated pressure gradient
Implementation Method 3
Administering the viral vector into the white matter below a targeted cortical region leads to axonal transport of the vector into overlying areas of the cortex
Data Source
Figure 1a~1j
Figure 2a~2c
Figure 3a~3f
AI summary
The present invention provides a viral vector for use in the treatment of neurological disorders, wherein the viral vector comprises a therapeutic agent and is being administered into the white matter of the brain in order to deliver the therapeutic agent to the cerebral cortex or to the cerebral cortex and spinal cord as well as providing methods for delivering therapeutic agents into the cerebral cortex or to the cerebral cortex and spinal cord comprising administering a viral vector comprising the therapeutic agent into white matter of the brain.